Srivastava Smriti, Luo Jun, Whalen Daniel, Robertson Katherine N, Jha Amitabh
Department of Chemistry, Acadia University, Wolfville, NS B4P 2R6, Canada.
Department of Chemistry, Saint Mary's University, Halifax, NS B3H C3C, Canada.
Molecules. 2025 Jan 19;30(2):415. doi: 10.3390/molecules30020415.
A concise, transition metal-free four-step synthetic pathway has been developed for the synthesis of tetracyclic heterosteroidal compounds, 14-aza-12-oxasteroids, starting from readily available 2-naphthol analogues. After conversion of 2-naphthols to 2-naphthylamines by the Bucherer reaction, subsequent selective C-acetylation was achieved via the Sugasawa reaction and reduction of the acetyl group using borohydride, which resulted into the corresponding amino-alcohols. The naphthalene-based amino-alcohols underwent double dehydrations and double intramolecular cyclization with oxo-acids leading to one-pot formation of a C-N bond, a C-O bond and an amide bond in tandem, to generate two additional rings completing the steroidal framework. A series of 14-aza-12-oxasteroids were synthesized using our developed synthetic strategy in moderate yields, and the structure of one of the final products, 12a-Methyl-11-phenyl-11,12a-dihydro-1-naphtho[2,1-d]pyrrolo[2,1-b][1,3]oxazin-3(2)-one, was further confirmed by single crystal X-ray crystallography.
已开发出一种简洁的、无过渡金属的四步合成途径，用于从易得的2-萘酚类似物开始合成四环杂甾体化合物，即14-氮杂-12-氧杂甾体。通过布赫勒反应将2-萘酚转化为2-萘胺后，通过菅泽反应实现后续的选择性C-乙酰化，并使用硼氢化物还原乙酰基，得到相应的氨基醇。基于萘的氨基醇与氧代酸进行两次脱水和两次分子内环化，导致依次一锅形成C-N键、C-O键和酰胺键，生成另外两个环，从而完成甾体骨架。使用我们开发的合成策略以中等产率合成了一系列14-氮杂-12-氧杂甾体，并且通过单晶X射线晶体学进一步证实了其中一种最终产物12a-甲基-11-苯基-11,12a-二氢-1-萘并[2,1-d]吡咯并[2,1-b][1,3]恶嗪-3(2)-酮的结构。
